Signalosome assembly by domains undergoing dynamic head-to-tail polymerization

Abstract

A key mechanism for guarding against inappropriate activation of signaling molecules is their weak affinity for effectors, which prevents them from undergoing accidental signal-transducing interactions due to fluctuations in their cellular concentration. The molecular devices that overcome these weak affinities are the signalosomes: dynamic clusters of transducing molecules assembled typically at signal-activated receptors. Signalosomes contain high local concentrations of protein-binding sites, and thus have a high avidity for their low-affinity ligands that generate signal responses. This review focuses on three domains - DIX (dishevelled and axin), PB1 (Phox and Bem1), and SAM (sterile alpha motif) - that undergo dynamic head-to-tail polymerization to assemble signalosomes and similar particles that require transient high local concentrations of protein-binding sites.